Identification of histocompatibility antigens and mechanism of action

George Snell, Jean Dausset and Baruj Benacerraf were awarded the the immune system differentiates between ‘self’ and ‘other’.

To identify the causes of transplant and blood transfusion rejection, George Snell studied the phenomenon in mice in the 1940s by conducting tumour transplants. By creating different strains of mice with different genetic make-up, he showed that transplant success was determined by histocompatibility antigens, markers on the cell membrane that identify if a cell is from the host. Snell also found genes that control these antigens in mice, which are grouped together within a limited region of the chromosome.

Jean Dausset then found the first histocompatibility antigen in humans by studying immune response following blood transfusions. Even though blood groups were already understood, recipients mounted an immune response against white blood cells from the donor. Through this work, he discovered the first human equivalent of a histocompatibility antigen. Dausset’s later work studying the antibodies of women and their children allowed him to find the genes for these antigens in humans. Further study revealed that the system is very similar in humans to that seen previously by Snell in mice. This has since led to screening for antigen similarity ahead of organ transplants, which has greatly increased the success rates.

Benacerraf studied the other side of the immune reaction and showed that the immune response to an antigen is controlled by genes. He found this by comparing the reaction of different strains of guinea pigs to the same antigen. The genes that he identified are located within the same region that determines the antigens, the major histocompatibility complex region.